From owner-radoncjc@net.bio.net Wed Jun 7 00:14:02 2000 Return-Path: Received: by mercury.hgmp.mrc.ac.uk (Postfix, from userid 110) id 90BF717B0F; Wed, 7 Jun 2000 00:13:59 +0100 (BST) Received: by mercury.hgmp.mrc.ac.uk (Postfix, from userid 60001) id 275B817B1E; Wed, 7 Jun 2000 00:13:58 +0100 (BST) To: radoncjc@net.bio.net From: Brian@hgmp.mrc.ac.uk, Goldsmith@hgmp.mrc.ac.uk, MD@hgmp.mrc.ac.uk Reply-To: radoncjc@net.bio.net Date: 6/6/00 4:01PM Subject: June 2000 Internet Radiation Oncology Journal Club (IROJC) Message-Id: <20000606231358.275B817B1E@mercury.hgmp.mrc.ac.uk> Sender: owner-radoncjc@net.bio.net Precedence: bulk June 2000 Internet Radiation Oncology Journal Club (IROJC) ------------------------------------------------------- Posting of references for review and discussion ------------------------------------------------------- The 61st collection of references suggested for attention and discussion by the IROJC's Board of Editors: Sarah Donaldson, M.D. Editor, Pediatric Radiation Oncology Robert Foote, M.D. Editor, Head and Neck / Skin Radiation Oncology Abram Recht, M.D. Editor, Breast Radiation Oncology Rich Hoppe, M.D. Editor, Reticuloendothelial System Radiation Oncology Dan Petereit, M.D. Editor, Gynecological Radiation Oncology Andrew Turrisi, M.D. Editor, Lung and Mediastinum Radiation Oncology Joel Tepper, M.D. Editor, Gastrointestinal and Soft Tissue Sarcoma Radiation Oncology Mack Roach, M.D. Editor, Genitourinary Radiation Oncology Glenn Bauman, M.D. Ph.D. Editor, Central Nervous System Radiation Oncology Rod Withers, M.D., D.Sc. Editor, Radiobiology James Hayman, M.D. Editor, Health Services Research George Chen, Ph.D. Editor, Radiation Biophysics ----------------------------------------------------- You're encouraged to critically review this set of references and respond by posting your comments to the IROJC readership at radoncjc@net.bio.net. Comments should be in compliance with IROJC commentary rules (see below). In the month that follows this posting of references, submitted comments will be delivered to the e-mail boxes of the IROJC readership. ------------------------------------------------------------ ARCHIVED IROJC material is available at http://www.bio.net/hypermail/radoncjc/ ------------------------------------------------------------ Commentary Rules: (1) Please cite the subject category in the header of your e-mail message, e.g., Subject: CNS 6/00. (2) Address the readership at large - not the Editor who suggested the reference. The Editor is under no obligation to respond to questions posed by the IROJC readership. (3) The Editor's selection is not necessarily an endorsement of the authors' conclusions. In fact, articles may be selected for criticism. (4) Comments posted to the Internet are public. Professional wording is prudent. (5) Comment only on journal articles that you have read recently, and please keep comments specific. (6) In order to minimize confusion, limit comments to the current month's list of references. (7) Please sign all comments and questions to the IROJC. By identifying yourself, you promote a more collegial and friendly environment! (8) Address to the Moderator (goldsmithb@radiological.com) private questions and comments which are not intended for IROJC posting and public reading. ****************** Peds: Donaldson 6/00 AU: Bacci G; Ferrari S; Bertoni F; Rimondini S; Longhi A; Bacchini P; Forni C; Manfrini M; Donati D; Picci P. TI: Prognostic factors in nonmetastatic Ewing's sarcoma of bone treated with adjuvant chemotherapy: analysis of 359 patients at the Istituto Ortopedico Rizzoli. SO: J Clin Oncol 2000 Jan;18(1):4-11. URL: http://www.jco.org/cgi/content/full/18/1/4 Abstract: PURPOSE: The identification of prognostic factors in patients with nonmetastatic Ewing's sarcoma could allow the use of risk-adapted therapeutic strategies of treatment. PATIENTS AND METHODS: Data on 359 patients with nonmetastatic Ewing's sarcoma of bone treated at a single institution between January 1979 and April 1995 were retrospectively considered. The influence of clinical, hematologic, therapeutic, and histologic parameters on event-free survival was assessed. RESULTS: By univariate analysis, the following features were found to be associated with a poor prognosis: male sex (P <.02), age older than 12 years (P <.006), fever (P <.0001), anemia (P <.0025), high serum lactate dehydrogenase (LDH) level (P <.0001), axial location (P <.04), radiation therapy only for local control (P <.009), type of chemotherapy regimen (P <.0001), and poor chemotherapy-induced necrosis (P <.001). After multivariate analysis, the adverse independent prognostic factors were male sex (P <.04), age older than 12 years (P <.001), fever (P <.0002), anemia (P <.02), high serum LDH level (P <.0003), axial location (P <.02), and type of chemotherapy regimen (P <.0003). When the multivariate analysis was restricted to surgically treated patients, the adverse independent prognostic factors were poor chemotherapy-induced necrosis (P <.0001), fever (P <.015), anemia (P <.02), and high serum LDH level (P <.025). CONCLUSION: The prognosis in cases of nonmetastatic Ewing's sarcoma is influenced by many different clinical and hematologic variables, all of which are to be considered when patients are being stratified according to the risk of relapse. In surgically treated patients, the most important prognostic factor is chemotherapy-induced necrosis. Editor's comments: A strength of this article is that it comes from an excellent center with outstanding expertise in malignant bone tumors, and reports a large number of patients. But it is a retrospective review; protocols evolve, followup is varied, and prognostic factors change. In univariate analysis, radiotherapy as local treatment was associated with a poorer outcome than seen with surgery, but this was not true in multi-variate analysis. Tumor size/volume, reported by almost all investigators, was not a prognostic indicator. The authors appropriately state that outcome is influenced by many variables; these variables are not static. The use of radiation in this study was selected for patients with unfavorable pelvic, sacral, and spine primary sites, whereas surgery was selected for the most favorable extremity tumors. No investigator has successfully avoided the selection bias which determines a patients local therapy - which is: response to chemotherapy, and accessible lesion. Those that respond well to induction chemotherapy and are surgically resectable are most frequently selected for resection. Those that don't respond well, or are not thought to be resectable, are sent for radiation. While we will never have a randomized study to compare local modalities, it remains that radiation, given to an appropriate dose and volume, is good treatment for non-metastatic Ewings sarcoma of bone. ****************** Head/Neck/Skin: Foote 6/00 No Reference Selected ****************** GYN: Petereit 6/00 AU: Peters WA 3rd; Liu PY; Barrett RJ 2nd; Stock RJ; Monk BJ; Berek JS; Souhami L; Grigsby P; Gordon W Jr; Alberts DS. TI: Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix. SO: J Clin Oncol 2000 Apr;18(8):1606-13. URL: http://www.jco.org/cgi/content/full/18/8/1606 Abstract: PURPOSE: To determine whether the addition of cisplatin-based chemotherapy (CT) to pelvic radiation therapy (RT) will improve the survival of early-stage, high-risk patients with cervical carcinoma. PATIENTS AND METHODS: Patients with clinical stage IA(2), IB, and IIA carcinoma of the cervix, initially treated with radical hysterectomy and pelvic lymphadenectomy, and who had positive pelvic lymph nodes and/or positive margins and/or microscopic involvement of the parametrium were eligible for this study. Patients were randomized to receive RT or RT + CT. Patients in each group received 49.3 GY RT in 29 fractions to a standard pelvic field. Chemotherapy consisted of bolus cisplatin 70 mg/m(2) and a 96-hour infusion of fluorouracil 1,000 mg/m(2)/d every 3 weeks for four cycles, with the first and second cycles given concurrent to RT. RESULTS: Between 1991 and 1996, 268 patients were entered onto the study. Two hundred forty-three patients were assessable (127 RT + CT patients and 116 RT patients). Progression-free and overall survival are significantly improved in the patients receiving CT. The hazard ratios for progression-free survival and overall survival in the RT only arm versus the RT + CT arm are 2.01 (P =.003) and 1.96 (P =. 007), respectively. The projected progression-free survivals at 4 years is 63% with RT and 80% with RT + CT. The projected overall survival rate at 4 years is 71% with RT and 81% with RT + CT. Grades 3 and 4 hematologic and gastrointestinal toxicity were more frequent in the RT + CT group. CONCLUSION: The addition of concurrent cisplatin-based CT to RT significantly improves progression-free and overall survival for high-risk, early-stage patients who undergo radical hysterectomy and pelvic lymphadenectomy for carcinoma of the cervix. Editor's comments: Peters et al. just published the fifth randomized trial in manuscript form that further supports the use of concurrent chemo-radiotherapy for patients with cervical cancer. Patients were randomized post-operatively to either radiation alone or concurrent chemo-radiotherapy if they met the following criteria: positive pelvic lymph nodes, positive margins or parametrial involvement. Pelvic radiotherapy was given to 49.3 Gy at 1.7 Gy/fx. If the high common iliac lymph nodes were positive, 45 Gy was given to the pelvis and para-aortic regions. No brachytherapy was permitted. Four cycles of cisplatin and 5-FU were delivered concurrently. At four years concurrent therapy improved the progression-free survival by 17% (63%, 80%) and survival by 10% (71%, 81%). As anticipated, more grade 3 and 4 hematologic and gastrointestinal toxicities were encountered in the combined modality group. It is remarkable that all five randomized cervical trials using platinum based chemo-radiotherapy demonstrated an approximate 10% improvement in survival compared to radiotherapy alone. Although more acute toxicities are encountered, the significant improvement in survival appears justified if patients are medically fit. The Peters Intergroup Study differed from the other randomized post-operative cervical trial that was published by Sedlis et al. (GOG #92). In GOG #92 only patients with high-risk cervical features and negative lymph nodes were studied. At 2 years, 21% of the surgery alone patients failed, compared to 12% of those radiated. The survival rates at 2 years were 79% in the surgery arm and 87% in the radiation arm -- P value not significant. A survival benefit most likely will be observed with longer follow-up since very few surgical recurrences are salvaged. What is the take home message from these studies? It appears that patients with negative pelvic lymph nodes and high-risk cervical features, as defined in GOG #92, should receive adjuvant pelvic radiotherapy, while patients with positive pelvic lymph nodes should receive concurrent chemo-radiotherapy. I personally think a brachytherapy boost should be strongly considered for the GOG #92 population, and those with positive margins and /or parametrial involvement. Reasons to consider a boost include a significant portion of failures occur at the vaginal apex, and little additional toxicity is encountered. However, until the failure patterns of both studies are further investigated, the role of a brachytherapy boost will most likely be institutional preference. It is of interest that only 2 years ago many IB cervical cancer patients were being managed very effectively with radiotherapy alone. Now, many will receive triple modality therapy. While there are certainly patients who have unforeseen adverse pathologic factors that require post-operative radiation, + chemotherapy, there are patients who could be spared surgery or triple modality therapy with equally effective results and less toxicity. For example, should a woman with a 4 cm poorly differentiated tumor undergo surgery? Also, should the surgeon proceed with a radical hysterectomy when positive lymph nodes are discovered? Hopefully, some attempt will be made to limit therapy while maximizing cure rates-both in practice and in future clinical trials. ****************** GI / Soft Tissue Sarcoma: Tepper 6/00 No Reference Selected ****************** CNS: Bauman 6/00 AU: Shaw E; Scott C; Souhami L; Dinapoli R; Kline R; Loeffler J; Farnan N. TI: Single dose radiosurgical treatment of recurrent previously irradiated primary brain tumors and brain metastases: final report of RTOG protocol 90-05. SO: Int J Radiat Oncol Biol Phys 2000 May 1;47(2):291-8. Abstract: PURPOSE: To determine the maximum tolerated dose of single fraction radiosurgery in patients with recurrent previously irradiated primary brain tumors and brain metastases. METHODS AND MATERIALS: Adults with cerebral or cerebellar solitary non-brainstem tumors From 7/94-7/98, 611 patients with newly diagnosed, unresected stage II-III NSCLC, KPS >70, & wt loss < 5% were enrolled in a phase III trial comparing two concurrent chemotherapy (CHM) and thoracic radiotherapy (TRT) regimens to a standard sequential CHM and TRT approach. The sequential arm (SEQ) included cisplatin (P) 100 mg/m-2 days (D) 1 and 29 & vinblastine 5 mg/m-2/weekly x 5 with 60 Gy TRT beginning D 50, and arm 2 used the same CHM with 60 Gy TRT beginning D 1 (CON-QD). Arm 3 employed P 50 mg/m-2 D 1, 8, 29, & 36 with oral VP-16 50 mg BID x 10 weeks 1, 2, 5, & 6 with 69.6 Gy in 1.2 Gy BID fractions beginning D 1 (CON-BID). Of the 597 analyzable pts, the rates of grade 3-4 non-hematologic (N-H) toxicity rates were higher with concurrent than sequential therapy, but late toxicity rates were similar. No difference in grade 5 toxicity rates is noted. With median and minimum potential follow-up times of 40 and 15 months respectively, results are as follows: ARM GR-3 Acute/Late N-H Tox Median Survival P value vs. SEQ SEQ 30% / 14% 14.6 mo CON-QD 48% / 15% 17.0 mo 0.08 CON-BID 62% / 16% 15.6 mo 0.31 These preliminary survival results for the concurrent platinum-based CHM and daily TRT arm (CON-QD) are quite promising and strongly support the continued investigation of concurrent CHM-TRT strategies for patients with locally advanced NSCLC. (Supported by RTOG U10 CA21661, CCOP U10 CA37422, Stat U10 CA32115 from the NCI). Editor's comments: The recent ASCO has some very interesting papers, and perhaps abstracts are too little fodder for this forum. But the freshest ideas are from these meetings. Without better papers to discuss, I call your attention to this abstract. Since the CALGB 8433 trial, first presented about 10 years ago at ASCO in New Orleans (just like this year) by Robert Dillman, the coinage "neoadjuvant" or in their words "protoadjuvant" (? cro-adjuvant) has held the day -- all neologisms for chemotherapy sequenced before local therapy with radiotherapy to the chest. Later, the French by Arriagada in the Red Journal and Le Chevalier in the JNCI showed that failure patterns proved that this method reduced distant metastasis, but NOT local failure rates. This year Furuse and colleagues from Japan wrote in JCO about the superiority of concurrent therapy over sequential therapy. However, they used MVP (mito, vindesine, platinum) -- a drug combination no longer in vogue. Curran and RTOG colleagues delivered an endorsement of this appraoch. They used a simple trial methodology, and complicated it a bit. The pure trial was the exact Dillman copy -- plat/velban followed by 60 Gy, vs. plat/velban concurrent with 60 Gy. (The third arm was 69.6 with the BID 1.2 scheme, and different drugs --- the third arm makes the randomization more complicated, and diluted the population -- complex and too complicated for a "good study", even agreed to by an anonymous RTOG statistician that I chatted up outside the Hall). The concurrent therapy was superior to the sequential (Median Survival 14.6 mo for sequential; 17 mo for the concurrent, 15.6 for the BID-concurrent), or at least trended in that direction. The toxicity is better with the sequential approach. However, the toxicity is not prohibitive. The real issues are that no one uses the Furuse or Curran/Dillman chemotherapy any longer. Everybody in the US uses Carbo/Taxol. Joan Schiller reported in the Plenary Session, similarly to Karen Kelley last year, that Carbo/Taxol is popular, but apparently no better than Platinum/Gemzar, Navelbine Platinum, or Taxotere Platinum -- the toxicity profiles vary, but the survival and responses are quite similar (see Proc ASCO 19: 1a, 2000). The differences between concurrent and sequential are modest, but now favoring concurrent because neither systemic control is adequate with current systemic treatment and local control is inadequate with just 60 Gy sequential or apparently concurrent. The problem is we do not know what is better. Current trends clearly point toward concurrent therapy outdistancing sequential therapy. If you or your patient is risk aversive, sequential therapy does not lag behind that far to say it is too timid therapy for the curative patient. ****************** GU: Roach 6/00 No Reference Selected ****************** Radiobiology: Withers 6/00 No Reference Selected ****************** Health Services Research: Hayman 6/00 No Reference Selected ****************** Radiation Biophysics: Chen 6/00 This month's multimedia physics contribution is a website from the Mayo Clinic on PC based software that processes and manipulates medical images. The URL is : http://www.mayo.edu/bir/BIR_home.html. Look at the first link - ANALYZE. "The Biomedical Imaging Resource at the Mayo Foundation has been involved since the early 1970's in the design and implementation of computer-based techniques for the display and analysis of multidimensional biomedical images. The algorithms and programs developed through this program have been integrated into a comprehensive software system called ANALYZEtm, useful in a variety of multimodality, multidimensional biomedical imaging and scientific visualization applications. The ANALYZEtm system features integrated, complimentary tools for fully interactive display, manipulation and measurement of multidimensional image data. It can be applied to data from many different imaging modalities, including CT, MRI, PET, SPECT, ultrasound and digital microscopy. The software runs efficiently on standard UNIX workstations without the need for special-purpose hardware. The software architecture permits systematic enhancements and extensions, and provides an effective shell for rapid prototyping of customized imaging applications solutions. The ANALYZEtm software system is continually evolving to extend its range of capabilities and expand its scope of applications, strongly influenced by collaborative research projects and the ANALYZEtm user community." (from their website) We recently acquired a copy of this software for research purposes (quite reasonable cost) and have used it to generate volume rendered images. The website describes ANALYZE in detail. I recommend this site for those interested in advanced medical imaging. While most of it is directed towards diagostic applications, the overlap with 3D planning is obvious. ****************** Brian J. Goldsmith, M.D. Moderator, IROJC From owner-radoncjc@net.bio.net Wed Jun 7 18:56:01 2000 Return-Path: Received: by mercury.hgmp.mrc.ac.uk (Postfix, from userid 110) id 1932A17B3F; Wed, 7 Jun 2000 18:55:58 +0100 (BST) Received: by mercury.hgmp.mrc.ac.uk (Postfix, from userid 60001) id 3832217B40; Wed, 7 Jun 2000 18:55:56 +0100 (BST) To: radoncjc@net.bio.net From: Brian@hgmp.mrc.ac.uk, Goldsmith@hgmp.mrc.ac.uk, MD@hgmp.mrc.ac.uk Reply-To: radoncjc@net.bio.net Date: 6/7/00 10:47AM Subject: June 2000 IROJC Lung/Mediastinum Erratum Message-Id: <20000607175556.3832217B40@mercury.hgmp.mrc.ac.uk> Sender: owner-radoncjc@net.bio.net Precedence: bulk The table in Curran et al, Prc ASCO 19: 484a abst 1891, formatted poorly in the June IROJC email and website. The following is a clarification of the table: In the sequential arm, Grade 3 Acute/Late non-hematologic toxity and median survival time were 30%/14% and 14.6 months, respectively. In the concurrent QD arm, Grade 3 Acute/Late non-hematologic toxity, median survival time, and the P value (vs. the sequential arm) were 48%/15%, 17.0 months, and 0.08, respectively. In the concurrent BID arm, Grade 3 Acute/Late non-hematologic toxity, median survival time, and the P value (vs. the sequential arm) were 62%/16%, 15.6 months, and 0.31, respectively. The abstract and table can be found on the web at the ASCO website: http://www.asco.org/cgi-bin/prof/abst00.pl?absno=1891&div=luc&year=00abstracts Brian Goldsmith, M.D. Moderator, IROJC